Paramagnetic rim lesions lead to pronounced diffuse periplaque white matter damage in multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) are an imaging biomarker in multiple sclerosis (MS), associated with a more severe disease.
Objectives: To determine quantitative magnetic resonance imaging (MRI) metrics of PRLs, lesions with diffuse susceptibility-weighted imaging (SWI)-hypointense signal (DSHLs) and SWI-isointense lesions (SILs), their surrounding periplaque area (PPA) and the normal-appearing white matter (NAWM).
Methods: In a cross-sectional study, quantitative MRI metrics were measured in people with multiple sclerosis (pwMS) using the multi-dynamic multi-echo (MDME) sequence post-processing software "SyMRI."
Results: In 30 pwMS, 59 PRLs, 74 DSHLs, and 107 SILs were identified. Beside longer T1 relaxation times of PRLs compared to DSHLs and SILs (2030.5 (1519-2540) vs 1615.8 (1403.3-1953.5) vs 1199.5 (1089.6-1334.6), both p  < 0.001), longer T1 relaxation times were observed in the PRL PPA compared to the SIL PPA and the NAWM but not the DSHL PPA. Patients with secondary progressive multiple sclerosis (SPMS) had longer T1 relaxation times in PRLs compared to patients with late relapsing multiple sclerosis (lRMS) (2394.5 (2030.5-3040) vs 1869.3 (1491.4-2451.3), p  = 0.015) and also in the PRL PPA compared to patients with early relapsing multiple sclerosis (eRMS) (982 (927-1093.5) vs 904.3 (793.3-958.5), p  = 0.013).
Conclusion: PRLs are more destructive than SILs, leading to diffuse periplaque white matter (WM) damage. The quantitative MRI-based evaluation of the PRL PPA could be a marker for silent progression in pwMS.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N.K. has participated in meetings sponsored by, received speaker honoraria or travel funding from Alexion, BMS/Celgene, Janssen-Cilag, Merck, Novartis, Roche, and Sanofi-Genzyme and held a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). V.S. has nothing to disclose. J.L. has nothing to disclose. L.H. has nothing to disclose. G.B. has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Novartis, Roche, Sanofi-Genzyme, and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis. G.K. has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, and received honoraria for consulting from Biogen. F.L. has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer, Biogen, Celgene/BMS, Janssen, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. B.K. has received honoraria for speaking and for consulting from Biogen, BMS-Celgene, Johnson & Johnson, Merck, Novartis, Roche, Teva, and Sanofi-Genzyme outside of the submitted work. No conflict of interest with respect to this study. P.S.R. has received honoraria for consultancy/speaking from AbbVie, Almirall, Alexion, Biogen, Merck, Novartis, Roche, Sandoz, Sanofi-Genzyme, and Teva and has received research grants from Amicus, Biogen, Merck, and Roche. T.B. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, BMS/Celgene, GSK, GW/Jazz Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi-Genzyme, Teva, and UCB. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, BMS/Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva). H.L. has received honoraria for lectures from Novartis, Biogen, ROCHE, Merck, and Sanofi-Aventis. A.D.-B.’s position as junior group leader for Translational Morphology in Neuroscience is supported by a research grant from Biogen. She has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene (BMS), Merck, Novartis, Roche, and Sanofi, and has received an unrestricted grant from Merck GmbH, an affiliate of Merck KGaA. S.H. has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen and Sanofi-Aventis.